Polyene compounds

ABSTRACT

Conjugated polyene dialdehyde compounds having 14-44 carbon atoms and mixtures thereof which are useful as coloring agents for foodstuffs, pharmaceutical preparations and cosmetic preparations and a method for preparing these dialdehydes including various intermediates in this method. This method is carried out by reacting a phosphonium salt of a conjugated aliphatic olefine having a terminal aldehyde radical with a conjugated aliphatic olefine having a terminal acetal linkage radical and a terminal aldehyde radical and thereafter hydrolyzing the reaction product to produce the dialdehyde. This dialdehyde may be further chain lengthened by reacting this dialdehyde with a phosphonium salt of a conjugated olefine having a terminal aldehyde radical, or by reacting with a vinyl ether or propenyl ether.

United States Patent [191 Gutmann et al.

POLYENE COMPOUNDS Inventors: Hugo Gutmann; Ulrich Schwieter,

both of Reinach, Switzerland Assignee: Hoftmann-La Roche Inc., Nutley,

Filed: Jan. 14, 1971 Appl. No.: 106,575

Related US. Application Data Division of Ser. No. 608,487, Jan. 11,1967, Pat. No. 3,577,464.

References Cited UNITED-STATES PATENTS V 6/1957 Birbeglia 260/488 3/1961Kimel 260/488 June 26, 1973 3,401,193 9/1968 Farressey 260/488 PrimaryExaminer-Lorraine A. Weinberger Assistant ExaminerVivian GarnerAttorney-Samuel L. Welt, Jon S. Saxe, Bernard S. Leon, William H.Epstein and George M. Gould [5 7] ABSTRACT Conjugated polyene dialdehydecompounds having 14-44 carbon atoms and mixtures thereof which areuseful as coloring agents for foodstuffs, pharmaceutical preparationsand cosmetic preparations and a method for preparing these dialdehydesincluding various intermediates in this method. This method is carriedout by reacting a phosphonium salt of a conjugated aliphatic olefinehaving a terminal aldehyde radical with a conjugated aliphatic olefinehaving a terminal acetal linkage radical and a terminal aldehyde radicaland thereafter hydrolyzing the reaction product to produce thedialdehyde. This dialdehyde may be further chain lengthened by reactingthis dialdehyde with a phosphonium salt of a conjugated olefine having aterminal aldehyde radical, or by reacting with a vinyl ether or propenylether.

4 Claims, NoDrawings POLYENE COMPOUNDS CROSS REFERENCE TO RELATEDAPPLICATION This application is a division of U.S. Pat. application Ser.No. 608,487, filed Jan. 11, 1967 now U.S. Pat. No. 3,577,464.

BACKGROUND OF THE INVENTION This invention relates to coloring agentsand the use of these coloring agents in coloring materials such asfoodstuffs, pharmaceuticals and cosmetics. This invention also relatesto a method of producing these coloring agents including intermediatesin the preparation thereof.

Of. the pigments of natural or synthetic origin which are suitable forcoloring foodstuffs, ,B-carotene and the apocarotenals derived fromnatural pigments have been found to be particularly useful. However,various disadvantages impose a limit on the general use of thesepigments. This is seen by the fact that the color tones achieved withthese pigments lie within a relatively narrow range which extends fromyellow-orange to yellow red. Intermediate tones, can of course, beobtained by mixing various components. However, such mixtures ofpigments are not color-constant when, as is frequently the case, theindividual components are unstable or differentially stable. Thesepigments also vary their color with increasing dilution. In the case ofcarotene, for example, an undesirable color-shift to a pale yellow isobserved with decreasing concentration. The desired saturated tints mayoften only be achieved by high concentrations, which are associated withhigh costs and are therefore uneconomical.

SUMMARY OF THE INVENTION In accordance with this invention, it has beenfound that when polyene dialdehyde compounds of the formula:

where X is an integer from to I, Y is an integer from O to 3 with theproviso that the sum of X and Y is an integer of at least one, ormixtures thereof when incorporated into foodstuffs, including beverages,pharmaceutical preparations and cosmetic preparations impart a widevariety of colors to these materials and do not possess many of thedisadvantages which are present with regard to ,B-carotene and theapocarotenals derived from natural pigments. The dialdehyde compounds inaccordance with this invention range from C 14 dialdehydes to C 44dialdehydes and range in color from yellow to violet. The lower membersof this series of compounds are colored intensive yellow, orange andraspberry red and the higher members are colored ruby red and violet.I-Ience, these new compounds extend the very small range of foodstuffpharmaceutical and cosmetic colors in a manner that has not beenachieved by the know coloring compounds.

Furthermore, these compounds have a high degree of stability and aredistinguished from other food coloring substances with related colorproperties by the fact that their pigment or coloring character is notinfluenced by the concentration of the compound in a solution. Solutionsof these substances or compounds surprisingly retain their tint unvariedeven when these compounds are greatly diluted. The compounds of formulaI are theredehyde) imparts a red color.

Furthermore, in accordance with this invention, the coloring agents offormula I above are prepared by reacting the phosphonium salt of theformula:

wherein R, R and R are selected from the group consisting of arylradicals containing from six to 16 carbon atoms, aralkyl radicalscontaining from seven to 16 carbon atoms and alkyl radicalscontainingfrom one to 16 carbon atoms, Z is an anion of a mineral acidand B is a conjugated olefinic radical containing from four to 14 carbonatoms and at least one methyl side chain,

with an organic aldehyde of the formula:

wherein R is a lower alkyl radical and B is a conjugated olefinicradical containing from four to 14 carbon atoms and at least one methylside chain, and thereafter hydrolyzing this reaction product to form adialdehyde of the formula:

wherein B and B are as above. This dialdehyde can further react, ifdesired, with at least 2 moles of the phosphonium salt of the formula:

Z RR"R"'P-CH B CHO wherein Z, R, R" and R are as above and B is aconjugatedolefinic radical containing from four to 14 carbon atoms andat least one methyl side chain, or, according to another alternative,with a vinyl ether or propenyl ether to produce a conjugated polyenedialdehyde of a high molecular weight.

DETAILED DESCRIPTION The coloring agents of formula I above, inaccordance with this invention, can be used to color any conventionalfoodstuff including beverages, fruits, vegetable preserves, marmalades,cream foods, confectionary, edible fats, cheese, fish products, pasta,soup powders, etc. Any conventional pharmaceutical preparation can becolored by compounds of formula I. Among the typical pharmaceuticalpreparations which can be colored in accordance with this invention areincluded {dragees, suppositories, gelatin capsules and syrups. Also anyconventional cosmetic preparation can be colored with the compounds offormula I above.

Among the conventional cosmetic preparations which .canbe colored inaccordance with this invention are included, toothpaste, skin creams,lipsticks and nonalcoholic mouthwashes. I

' ount sufficient to impart a color to the material. Generally, it ispreferred that the foodstuff, pharmaceutical and cosmetic preparationcontain from about 0,000000l parts by weight to about 0,1 parts byweight of compound of formula I above based on the weight of thefoodstuff, pharmaceutical and cosmetic preparation. It is suitable tomake the amount of compounds of formula I to be added dependent on thenature of the preparations to be colored. Thus, for coloring foodstuffs,it is advantageous to add from about 0,0000001 parts by weight to about0,0001 parts by weight of compound of formula I based on the weight ofthe preparation (e.g. about 0,000002 parts by weight to about 0,000005parts by weight are used for coloring beverages, such as carbonatedorange beverages, about 0,00001 parts by weight to about 0,000025 partsby weight are used for coloring ice creams, confectionary etc. and0,00001 parts by weight to about 0,00005 parts by weight are used forcoloring yoghurts). In the cosmetic field preferably about 0,0000001parts by weight to about 0,05 parts by weight of compound of formula Iare used based on the weight of the cosmetic preparation (e.g. fromabout 0,001 parts by weight to about 0,05 parts by weight are used forcoloring lipsticks and from about 0,0000001 parts by weight to about0,00007. parts by weight are used for coloring 'creams such as skincreams,toothpaste etc.). Pharmaceutical preparations, such assuppositories and'syrups preferably contain from about 0,000005 parts byweight to about 0,001 parts by weight based on the weight'of thepreparation. In case of coloring dragees, the coating suitablycontainsfrom about 0,00l mg to about 0,1 mg of compound of formula I percm surface of the dragees. Although greater amounts than the parts byweight of the compound of formula I specified above can be incorporatedinto the foodstuff, pharmaceutical or cosmetic preparation, however,these high amounts are seldom utilized since no additional benefits,asfar as color is concerned, is obtained by utilizing such large amountsof the compounds of formula I above.

The polyene compounds of formula I can be employed for coloringfoodstuffs, pharmaceuticaland cosmetic preparations both in the originalcrystallineform and in a particular water-soluble form.

ple, be dissolved in oils without further ado. Prior to the addition ofthe pigment, hard or soft fats are conveniently liquified by heating.Brushable fats may also be colored by kneading-in an oilpigment-solution. Marzipan, which for example, is thoroughly kneadedwith a solution of the polyene compound of formula I in almond oil, canalso be colored in the same way. Colored suppositories and lipstickscan, for example, be manufactured in such a way that the polyenecompound used as the pigment is stirred into the liquified carrier massprior to filling into the molds.

For coloring fat-poor or fatless substances, there is generally used awater-dispersible form of the polyene compounds of formula I. Thepreparation of these compounds in water-dispersible form can be carriedout by any of the techniques disclosed in U. S. Pat. No. 2,861,891,Bauernfeind et al. and U. 8. Pat. No. 3,110,598, Muller et a1.Theseinclude dissolving the polyene compounds of formula I in a suitablesolvent, homogenizing the solution (together with a stabilizer and asolubilizing or emulsifying agent if required, as

well as with an animal or vegetable fat if desired) with water in' thepresence of a protecting colloidand evaporating the emulsion formed todryness under reduced pressure.

Any conventional organic solvent capable of dissolving the compound offormula 1 above, can be utilized. These solvents include volatilehalogenated hydrocarbons such as, for example, chloroform, carbontetrachloride, methylene chloride, etc. Any conventional antioxidativelyactive stabilizers can be utilized. These antioxidants includetocopherols, 2,6-ditertbutyl-4- hydroxytoluene [Bl-IT],butyl-hydroxyanisole [BHA].

The salts of fatty acid esters of ascorbic acid (e.g. the sodium salt ofascorbyl palmitate), inter alia, have been found to be active assolubilizing agents. Any of the conventional solubilizing agents can beutilized in accordance with this invention. Concerning emulsifyingagents, any conventional emulsifyingagent can be utilized in accordancewith this invention. The polyoxyethylene derivatives of sorbitananhydrides partially esterified with fatty acids [Tweens] ornon-ionogenic derivatives of fatty compounds with polyoxyethylenederivatives [Crernophores] are, for example, usable. The protectingcolloids inwhich the compounds of formula I are emulsified or dispersedinclude any of the conventional water soluble gelable colloids. Gelatin,dextrin, pectin, tragacanth, guar (especially in the presence ofsaccharose, glycerin, s'orbitol), have, for example, been found to beuseful as protecting colloids. The color brilliance of the aqueoussolutions can be increased by the addition of any animal fat (e.g. beeftallow) or vegetable oil (e.g. groundnut oil).

The C 14 to C 44 dialdehydes of this invention can be prepared bybuilding up the molecule through chain-lenghthening of suitablealdehydes. The lowest member 4,9-dimethyl-dodeca-pentaene-(2,4,6,8 ,10)-dial-( 1,12) [C l4-dialdehyde] is obtained by the condensation of2,7-dimethyl-octa-triene-(2,4,6)-dial- (l,8)-diacetal with two moles ofvinyl ether.

In general, the dialdehydes of formula I above can be prepared bybuilding through chain lengthening by wherein A is a conjugated four to14 carbon radical having one acetylene linkage therein and having atleast one, preferably from one to six methyl side chains, B is the sameas A with the one acetylene linkage reduced to an olefinic linkage, R isa hydrogen or lower alkyl radical containing from one to seven carbonatoms, R; is a lower alkyl radical containing from one to seven carbonatoms, R, R", R being an aryl radical containing six to 16 carbon atoms,an aralkyl radical containing from seven to 16 carbon atoms or a loweralkyl radical containing from 1 to 7 carbon atoms and Z is an anion of amineral acid, eg Br, Cl, l-- and HSO The reduction of compounds of theformula II above to compounds of formula III above can be effected bycatalytic hydrogenation in the presence of a catalyst which selectivelyreduces only the triple bond (acetylene linkage) to a double bond. Forexample, compounds of formula II above can be catalyticallyhydrogenated, in an inert solvent such as ethyl acetate, toluene orpetroleum ether, in the presence of a selective hydrogenation catalyst,e.g., a palladium-lead catalyst in the presence of quinoline, of thetype disclosed in the publication Helvetica Chimica Acta, 35,446 (1952).

The conversion of compounds of the formula III above to compounds of theformula lV-b above, is carried out by first hydrolyzing the esterlinkage in the compounds of formula In above to form the hydroxycompound of formula IV-a above which is oxidized to the aldehyde offormula IV-b. During this procedure, the aldehyde group in formula IIIabove is protected during the oxidizing step (e) by means of its beingconverted to an acetal group anytime before oxidation.

Compounds of formula III are converted into compounds of the formula V-aby first hydrolyzing the ester group in the compounds of formula III tothe hydroxy compound of formula V and thereafter reacting the hydroxycompound of formula V above, if desired, after its conversion into ahalogeno compound, with a phosphine compound of formula X, as in step(f). In carry-v ing out the reaction of step (f), compounds of formula Vor halogeno derivatives thereof are reacted with a phosphine of theformula X in an inert solvent (such as, for example, a lower alkanolsuch as methanol or ethanol) in the presence of a proton donor or withan acid addition salt of the phosphine of formula X or a diarylmonoalkylphospine. Proton donors which can be employed in the above processinclude inorganic acids such as hydrohalic acids or sulfuric acid. Inthis manner, the compounds of the formula V-a are formed.

During the reaction of step (f), it is preferable to first form theacetal of compound V, by means of utilizing a conventional acetalforming agent, so as to protect the aldehyde group of compound V duringits reaction with the phosphine of formula X. In this case the acetalfunctional group would be converted to the corresponding aldehyde groupby hydrolysis during step (h).

Compound of formula lV-b and compounds of formula V-a or an acetalthereof can be reacted as in step (g) to form the chain lengthenedcompounds of formula VI. This reaction is preferably carried out in thepresence of a solvent, i.e., an organic solvent substantially inerttothe reactants such as a lower alkanol solvent having from 1 to 7carbon atoms, i.e., methanol, ethanol, etc. di-methylformamide,acetonitrile or benzene. The preferred solvents are methanol andbenzene. The reaction is conducted in the presence of a strong base,such as an alkali metal hydride, e.g., sodium hydride, potassiumhydride, an alkali metal amide, e.g., sodium amide, alkali metal-loweralkoxide,

preferably sodium methoxide, or a solution of an alkali metal hydroxidein a lower alkanol, e.g., KOH in methanol. This reaction can be carriedout at room temperature. However, temperatures as high as the refluxtemperature of the solvent or as low as the freezing point of thesolvent can be effectively employed. In carrying out the reaction ofstep (g), one mole of the compounds of formula lV-b can be reacted withone mole of the compound of formula V-a if desired. However, a molarexcess of the compound of formula lV-a or the compounds of formula V-acan be utilized.

I pound of formula VII above with the phosphonium salt of compound V-aabove as in set (i). This reaction can be carried out in the same manneras step (g) except that at least two moles of the compound of formulaV-a or of an acetal thereof should be utilized per mole of the compoundsof formula VII above. Alternatively, compounds of formula VII above canbe chainlengthened by reaction with a vinyl ether or a propenyl ether,preferably a lower alkyl ether.

In carrying out the reaction of step (g), a phosphonium salt containingthe same B-radical as the B-radical in compound lV-b can be utilized.However, if desired, the phosphonium salt containing a differentlB-radical than the B-radical in compound IV-b can be utilized incarrying out step (g) In carrying out step (i), the phosphonium saltthat is utilized can be the same phosphonium salt as thatused in step(g) or a different phosphonium salt than is utilized in step (g).

This invention is further illustrated by the following examples whichare illustrative but not limitative thereof.

EXAMPLE 1 Preparation of 2,6, l 1 lS-tetramethyl-hexadecaheptaene-(2,4,6,8,l 12,l4-dial-(l,l6) [C 20dialdehyde].

, A. Preparation of 8,8-dimethoxy-3,7-dimethyl-octatrien-(2,4,6)-al-l.

lated, but is directly alkaline-saponified. A solution of 37.7 g. ofsodium hydroxide in 34 ml. of water and 180 ml. of methanol is addeddropwise thereto with stirring at 0-5 C. within 20 minutes. The reactionmixture is further stirred at 5-l0 C. for 15 minutes, immediatelythereafter poured into 2.5 liters of icecold 5 percent by weightpotassium hydrogen carbonate solution and extracted twice with ether(500 and 800 ml.). The ether phase is washed twice with fresh potassiumhydrogen carbonate solution and dried over potassium carbonate.

The hydroxy acetal {absorption maximum (in petroluem ether) 276 mu]containing ether solution is subsequently treated with 300 g. ofmanganese dioxide and stirred or shaken at C. for 60 hours, thenfiltered and evaporated. The residual oil is taken up in 10 ml. ofpetroleum ether (boiling range 40-45 C.) and cooled in the ice-bath forsix hours. The orange-yellow all trans.8,8-dimethoxy-3,7-dimethyl-octa-trien- (2,4,6)-al-(1) crystallizing outmelts at 5 758 C. after recrystallization from petroleum ether:absorption maxima (in petroleum ether) 300 (shoulder), 313,327 mu; E1380, 2000, 1780.

B. Preparation of (3,7-dimethyl-8-oxo-octatrien- (2,4,6)-yl)-triphenyl-phosphonium bromide.

A mixture of 10.5 ml. of dimethylformamide and 45 ml. of methylenechloride is treated with stirring at 20 C. with 6.5 ml. of phosphoroustribromide and thereupon within 20 minutes with a 'solution of 16.6 g.of 8-hydroxy-2,6-dimethy1-octa-trien-(2,4,6)-al-( l) in 25 ml. ofmethylene chloride. The reaction mixture is stirred at l0 C. for onehour, then poured in icewater and extracted with 300 ml. of ether. Theether extract is washed twice with ice-water, three times with I Theice-cold 10 percent potassium hydrogen carbonate solution and twice withice-water, briefly dried over sodium sulphate and immediately evaporatedunder re duced pressure at 20 C. The residual 8-bromo-2,6-2,6-dimethyl-octa-trien-(2,4,6 )-al-( l crystallizes after trituration witha little ether. M.p. 6870 C; absorption maximum (in petroleum ether) 311mu. Without further purification, the unstable compound is immediatelydissolved in 50 m1. of methylene chloride and treated with 26 g. oftriphenyl-phosphine. In doing so, the solution warms up to boiling.After 1 to 1.% hours, 200 ml. of acetic acid ethyl ester are slowlyadded while scratching with a glass rod. The(3,7-dimethyl-8-oxoocta-trien-( 2,4,6 )-yl )-tripheny1-phosphoniumbromide crystallizing out is filtered off in the cold after standing for12 hours. M.p. 203-205 C; absorption maximum (in ethanol) 315 mp; E fi970.

C. Preparation of dialdehyde.

60 g. of (3,7-dimethyl-8-oxo-octatrien-(2,4,6)-yl)-triphenyl-phosphonium bromide in 160 ml. of abs. methanol are treatedwith 20 ml. of orthoformic acid etrimethyl ester and a solution of 0.1g. of p-toluenesulphonic acid and 0.1 ml. of percent phosphoric acid in20 ml. of abs. methanol and allowed to stand at room temperature for 18hours. The reaction mixture is thereafter treated with 2 ml. of pyridineand subsequently simultaneously with a solution of 21 g. of 8,8-dimethoxy-3,7-dimethyl-octa-trien-( 2,4,6 )-al-( 1 in ml. of abs.benzene and a sodium methylate solution from 4 g. of sodium and 50 ml.of abs. methanol. The mixture is heated at 50 C. for four hours, thencooled and, after the addition of 70 g. of ice, partitioned betweenpetroleum ether (boiling range 4045 C.) and 85 percent methanol. Thepetroleum ether phase is washed several times with water, dried andevaporated. The residual crude 1,1,16,16- tetramethoxy-2,6, 1 1 1S-tetramethylhexadecaheptaene-(2,4,6,8,l0,12,14) is dissolved in 300 ml.of acetone and, after the addition of 15 ml. of l-N sulphuric acid,heated to boiling for 30 minutes.

2,6,1 l,15-tetramethyl-hexadecaheptane- (2,4,6,l0,12,l4)-dial-(1,16)which separates out melts at 19l C. after recrystallization from aceticacid ethyl ester; violet, metalically shining leaflets; absorptionmaxima (in chloroform) 267, 455, 483 mu; E 580, 3970, 3840.

By extraction with methylene chloride and isomerisation by exposure tolight in the presence of iodine, further fractions of this aldehyde maybe obtained from the filtrate.

According to the same mode of procedure described above, there canfurther be manufactured:

from 2 mol of (3-methyl-6-oxo-hexa-dien-(2,4)-yl)- triphenyl-phosphoniumbromide and 1 mole of 2,7- dimethyl-octa-trien-(2,4,6)-dial-( l,8) therewas produced 4,8,13 l 7-tetramethyl-eicosa-nonaene-(2,4,6,8,10,l2,14,l6,18)-dial-( 1,20) [C .,-dialdehyde]; violet needles:m.p: 226-227 C; absorption maxima: (in chloroform) 300, 492, 523 mu; E,660, 3750, 3460, from 2 mole of (3,7-dimethyl-8-oxo-octa-trien-2,4,6)-yl) triphenyl-phosphonium bromide and l mole of2,7-dimethyl-octa-triene-(2,4,6)-dial-( 1,8) there was produced 2,6,10,l5,l9,23-hexamethyl-tetracosaundecaene-(2,4,6,8,10,12,14,16,18,20,22)-dial-(1,24) [Cg -dialdehyde]; violet needles; m.p. 233235 C.; absorptionmaxima: (in chloroform) 329, 520, 552 mu; E,,,,, 745, 3590, 3050, from 2mole of (3,7- dimethyllO-oxo-deca-tetraen-( 2,4,6,8 )-yl)-triphenyltrien-(2,4,6)-y1)-triphenyl-phosphonium bromide and 1 mole of2,6,11,15-tetramethyl-hexadecaheptaene- (2,4,6,8,l0,12,14)-dial-( 1,16),there was produced -2,- 6,10, 14,1 9,23 ,27,3l-octamethyl-dotriaconta-pentadecaene-(2,4,6,8,10,12,l4,16,18,20,22,24,26,28,30)-dial-(1,32) [C -dialdehyde]; violet crystals; m.p. 26l- -263 C.;absorption maxima (in chloroform) 380, 556 my; E 810, 2770.

Examples 2 and 3 illustrate the preparation of starting materials forthe above which are not known.

EXAMPLE 2 Preparation of [3-methyl-6-oxo-hexa-dien-2 ,4yl]-triphenyl-phosphonium bromide.

(3-methyl-6-oxo-hexa-dien-( 2,4 )-yl )-triphenylphosphonium bromide canbe manufactured in an advantageous manner as follows:

42.5 g. of 6-hydroxy-4-methyl-hexa-dien-(2,4 )-a1-( 1) is reacted with21.5 ml. of phosphorous tribromide and extracted with ether in themanner described in part B of Example 1. The ether extract whichcontained the unstable 6-bromo-4-methyl-hexadien-(2,4)-al-(1) is,however, not evaported but remains in a cold state and is treated with asolution of 88 g. of triphenylphosphine in 100 ml. of methylenechloride. The (3- methyl-6-oxohexa-dien-(2,4)-yl)-triphenylphosphoniumbromide, initially oily, crystallized after tritaration. Thisphosphonium bromide salt separates out after standing at roomtemperature for two hours. The salt is recrystallized from a mixture of350 ml. of methylene chloride and 1.1 liters of acetic acid ethyl ester.M.p. 200-202 C. (dec.); absorption maxima (in ethanol) 268 (shoulder),274 mu; E =6l0, 630.

EXAMPLE 3 Preparation of [3,7-dimethyl-10-oxo-deca-tetraean-(2,4,6,8)-yl]- triphenyl phosphonium bromide.

A. Preparation of 10 -acetoxy -4,8 dimethyl-decatrim-(2,4,8)yn-(6)-al-1.

280 g. of 8-acetoxy-1,1-diethoxy-2,6-dimethyl-octadien-(2,6)-yne-(4) wasdissolved in 300 ml. of benzene and treated dropwise at 30-35 C.simultaneously with 85 g. of ethyl vinyl ether and 50 ml. ofa 10 percentsolution of anhydrous zinc chloride in acetic acid ethyl ester. Thereaction solution is left to stand at room temperature for 18 hours.Subsequently, 75 g. of anhydrous sodium acetate in 750 ml. of 87 percentacetic acid are added. Then it is heated to 95 C., held at thistemperature for four hours, poured on five liters of icewater andextracted with ether. The ether extract is washed with sodium hydrogencarbonate and neutralized with water, dried over sodium sulphate andevaporated. The residue is dissolved in 135 ml. of ether and cooled to-20 C. The l-acetoxy-4,8-dimethyl-deca-trien- (2,4,8)-yn-(6)-al-( lwhich crystallizes out melts at 3 l-32 C. U.V. maxima (in petroleumether) 310 (shoulder), 325, 342 mu; E 1350,1590, 1355.

B. Preparation of -acetoxy-4,8-dimethyl-deca-tetraen-(2,4,6,8)-al-( l 57g. of lO-acetoxy-4,8-dimethyl-deca-trien-(2,4,8)- yn-(6)-al-( l) weredissolved in 300 ml. of toluene and,

after the addition of Lindlar catalyst [Helv.-Chim.- Acta 35 (1952) 446]and 0.5 ml. of quinoline, hydrogenated up to the uptake of 1.05equivalents of hydrogen. The catalyst is filtered off. The filtrate issuccessively washed with 0.5-N sulphuric acid, potassium hydrogencarbonate solution and water, dried over sodium sulphate and treatedwith a solution of 0.2 g. of iodine in 50 ml. of toluene. The toluenesolution is left to stand at room temperature for 18 hours. It issubsequently successively washed with 5 percent sodium thiosulp atesqutip a er dried o er sqslium qlph and evaporated under reduced pressure.The residue is taken up in 30 ml. of isopropyl alcohol and cooled to 20C. The 10-acetoxy-4,S-dimethyl-deca-tetraen- (2,4, 6,8)-a1-( l) whichcrystallizes out melts at 64-66 C. U.V. maxima (in petroleum ether) 318,333, 350 mp4 E 1790, 2860, 2700.

C. Preparation of 10-hydroxy-4,8-dimethyl-deca-tetraen-(2,4,6,8)-al-l.

22.3 g. of finely powderedl0-acetoxy-4,8-dimethyldecatetraen-(2,4,6,8)-al-(l) are suspended in ml.of methanol and treated with vigorous stirring at 0-2 C. within 15minutes with a solution of 4 g. of sodium hydroxide in 4 m1. of. waterand 40 ml. of, methanol. The reaction mixture is further stirred at 0for 10 minutes, adjusted at this temperature to pH 7-8 with alcoholichydrochloric acid and evaporated under reduced pressure at ca 30 C. Theresidue was partitioned between methylene chloride and water. Themethylene chloride phase was washed with potassium hydrogen carbonatesolution and water, dried over sodium sulphate and evaporated. Theresidue was dissolved in 1.5 liters of boiling ether. The solution wasconcentrated up to incipient crystallization and cooled to -20 C..

The 10-hydroxy-4,8-dimethyl-deca-tetraen- (2,4,6,8)-al-( 1) formsorange-colored crystals. M.p. 103-105 C. [after sublimation: l04105 C.]absorption maxima (in petroleum ether) 319, 334, 351 mu; E 2160, 3360,3170.

D. Preparation of phosphonium salt.

The aldehyde prepared in part C was reacted with phosphorous tribromideand triphenyl phosphine to form [3 ,7-dimethyl- 1 0-oxo-deca-tetraen-(2,4,6 )-y1]- triphenyl-phosphonium bromide in the manner of part B ofExample 1. The melting point of this compound was 202204 C. (dec.);absorption maximum (in ethanol) 354 mu E 1060.

Examples 4 through 19 are directed to the use of the compounds offormula I above as coloring agents in foodstuffs, pharmaceutical andcosmetic preparations.

EXAMPLE 4 Manufacture of canary-yellow colored dragees 10,000 drageekemals each of 150 mg. are coated white up to a kernel weight of mg.with sugar syrup, starch and talc.

30 g. of color preparation containing 300 mg. of the C -dialdehydedisclosed above are soaked with 30 g. of water, combined with a solutionof 330 g. of sugar and 135 g. of water which has been heated to boilingand subsequently cooled to 60-70 C., and homogenized. The hollow coloredsugar solution is applied little by little to the white-colored drageesin the rotating coating-pan, sprayed with cold air. The dragees arepolished in the usual manner. *The color layer of one dragee (weight 225mg., diameter 1 cm., thickness 3mm.) contains 0.03 mg. of C -dialdehyde.

The water-soluble preparation employed as colordonor is, for example,manufactured as follows:

1. g. of a polyene compound of formula I are dissolved in 100 ml. ofchloroform and together with 100 mg. of tocopherol, 2g. of arachis oiland 2 g. of ascorbyl palmitate introduced into a solution of 60g. ofgelatin, 35 g. of sugar and 0.5 g. of calc. soda in 250 ml. of water andhomogenized. The colored chloroformcontaining gelatin emulsion is pouredon a metal sheet and subsequently evaporated in vacuum. The dry productis broken into small pieces.

EXAMPLE 5 Manufacture of lemon-yellow confectionery l. g. of commercialfondant mixture is homogenously mixed on a roller frame with a solutionof 1.5 g. of color preparation containing mg. of the C -dialdehydedisclosed above in 5 ml. of water. In order to achieve the desiredfluidity of the mass, either invert-sugar syrup or powdered sugar isworked in as required. After heating the colored fondant, the pureyellow glaze is applied to articles of confectionary or poured intostarch molds. The lemon-yellow fondant fillings which solidify inthe'starch molds are freed from starch dust and covered with chocolate.

EXAMPLE 6 EXAMPLE 7 Manufacture of lemon-yellow caramels 1.5 g. of colorpreparation containing 15 mg. of the C -dialdehyde, disclosed above, isdissolved in 5 ml. of water and added to 1 kg. of bon-bon mixturetowards the end of the cooking process or during the subsequentprocessing and homogeneously worked in.

EXAMPLE 8 Manufacture of egg-yellow colored fats and oils 5. mg. of theC -dialdehyde prepared in Example 1 are dissolved warm in 1 liter of oilor fat, a beautiful egg-yellow coloring being achieved.

EXAMPLE 9 Manufacture of yellow-orange colored pasta 1 kg. of hardwheat-grain is intimately mixed in a mixing drum with 300-350 ml. ofwater in which 0.5 g. of color preparation containing 5 mg. of the Cdialdehyde prepared in Example 1 have been dissolved. The moist, spongymass is brought into the desired form of pasta through suitable nozzlesand dried.

EXAMPLE 10 Manufacture of carbonic acid-containing yelloworange coloredcitrus soft drinks I 4 g. of color preparation containing 40 mg. of Cdialdehyde prepared in Example 1 are dissolved in 20 ml. of warm waterand homogenized with 100 g. of orange'concentrate. After the addition ofcitric acid and sugar syrup, the colored orange concentrate is dilutedto 10 liters with carbonic acid-containing water and filled into bottleshaving stirrup-closures.

EXAMPLE 1 1 Manufacture of orange-red colored suppositories 100 g. ofsuppository mixture are heated with 100 mg. of the crystallized C-dialdehyde prepared in Example 1 up to complete solution of thepigment. a-Tocopherol, BHT, BHA, gallates etc. can be admixed asantioxidants. After working-in the active substance, the orange-redfatty-mass is poured into the usual molds and allowed to cool.

EXAMPLE 12 Manufacture of red colored gelatin capsules 10 g. of colorpreparation containing I00 mg. of the C -dialdehyde prepared in Examplel are dissolved warm in 30 ml. of water and mixed with a hot gelatinsolution consisting of 650 g. of gelatin, 250 g. of glycerin (which canalso be partially replaced by sorbitol or other carbohydrates) and 800g. of water. The gelatin capsules are manufactured in the usual way,according to the dipping or press process, from this gelatin solution.

EXAMPLE 13 EXAMPLE 14 Manufacture of red colored gelatin foods 2. ofcolor preparation containing 20 mg. of the C dialdehyde prepared inExample 1 are dissolved in 6 ml. of warm water and stirred into oneliter of the warm, liquid gelatin solution consisting of the usualingredients. The solution is poured into molds and allowed to cool.

The same amount of pigment powder can also be mixed dry with the gelatinpudding powder sufficient for 1 kg. of prepared gelatin pudding. Thepigment particles dissolve, red colored gelatin desserts being obtained.

EXAMPLE 15 Manufacture of a reddish pastel-colored daytime cream 1 g. ofcolor preparation containing 10 mg. of the 'C -dialdehyde prepared inExample 1 is dissolved in 65 ml. of warm water. The solution isemulsified into a salve base which consists of 15 g. of cetyl alcoholand octadecyl alcohol, 3 g. of spermacetti l g. of butyl stearate, 1 g.of lanolin, 5 g. of CETIOL, 2.8 g. of COROL, 8 g. of glycerin orpropyleneglycol and 0.5 g. of perfume oil composition.

EXAMPLE 16 Manufacture of a bordeauX-red pudding mixture 2 g. of colorpreparation containing 20 mg. of the C -dialdehyde prepared in Example 1are admixed with the pudding powder which is sufficient for 1 liter ofready-prepared pudding and [the mixture] is further processed as usualby stirring or boiling up with milk.

EXAMPLE i 7 Manufacture of bordeaux-red colored yogurt 2. g. of colorpreparation containing 20 mg. of C dialdehyde prepared in Example 1 aredissolved warm in 5 ml. of water, mixed with one liter of milk andprocess'ed to [give] yogurt in the usual manner.

EXAMPLE 1 8 Manufacture of a bordeaux-red marzipan mixture- EXAMPLE 19Manufacture of a ruby colored toothpaste 0.5 g. of pigment powdercontaining mg. of C dialdehyde prepared in Example 1 are dissolved in 2ml. of water and homogeneously worked into 100 g. of

white toothpaste of the usual composition. If desired, the same pigmentpreparation can also be added to the raw materials dissolved in water orconverted into a paste with water.

EXAMPLE 20 This Example is directed to preparing 8-acetoxy-2,6-dimethyl-octa-trien-(2,4,6)-al-( 1) which is utilized as a startingmaterial in Example 1.

A. Preparation of ether.

175 g. of crude 5-( l-methoxy-1-methylethoxy)-3- methyl-pent-3-en-l-yneare introduced in a rapid stream into a solution of lithium amide inliquid ammoma.

The ammonia-alkaline lithium amide solution can be manufactured asfollows:

0.5 g. of finely divided lithium are introduced with stirring into 600ml. of liquid ammonia. After the addition of 0.5 g. of a iron (lll)nitrate, compressed air is led into the solution for a few seconds. Assoon as the blue color of the solution has disappeared, a further 7.1 g.of finely divided lithium are added. The evaporating ammonia iscondensed in a condenser charged with acetone/dry ice and led back tothe reaction mixture. [The mixture] is stirreduntil the blue colordisappears [15 to 60 minutes] The dark clear reaction solution isstirred for 90 minutes, then treated with 170 ml. of dry toluene andimmediately subsequently with l 14 g.. of 3-ethoxy-2- methylacrolein ina rapid stream and further stirred for l 30 minutes. The mixture issubsequently neutralized by the addition of 80 ml. of glacial acetic in200 ml. of toluene. The acid solution is conveniently addedthrough adropping funnel of which the exit tube dips into the reaction mixture.The ammonia is evaporated off, with stirring, until the temperature inthe reaction vessel has risen to 40 C. The toluene is subsequentlydistilled off under reduced pressure. The residual l-ethoxy-8-( 1-methoxy-l-methylethoxy)2,6-dimethyl-octa-2,6-dien- 4-yn-3-ol is alight-brown oil. U.V. maximum [in ethanol]; 228 m;1.;e 18000; n 1.5120;d 1.002.

The 5-( l-methoxy-methylethoxy)-3-methyl-pent-3- en-l-yne employed asstarting compound can be manufactured as follows: 96 g. of3-methyl-pent-2-en-4-yn-1- 01 are, after the addition of 0.5 m1. of percent methyl alcoholic p-toluenesulphonic acid, trated'with stirring andcooling at 5 to C. with 79 g. of isopropenyl methyl ether. The acetal isnot isolated, but further processed directly.

B. Preparation of hydroxy compound.

270 g. of 1-ethoxy-8-(1-methoxy-1-methylethoxy)-2,6dimethyl-octa-2,6-dien-4-yn-3-ol are dissolved in 400 ml. of tolueneand, with cooling and strong stirring, treated with 50 ml. of 2 percentsulphuric acid and 50 ml. of methanol, in doing which the temperatureshould not exceed 25 C. The reaction mixture is subsequently stirred at20 to 25 C. with nitrogen gassing for two hours. The toluene phase isseparated, washed with 400 ml. of a 10 percent aqueous sodium sulphatesolution and subsequently with 400 ml. of a 5 percent sodium hydrogencarbonate solution. The aqueous phases are separated and once moreshaken out with 100 ml. of toluene. The combined toluene extracts areconcentrated at 50 C. to a volume of 400 ml. The 2,6- dimethyl-8hydroxy-octa-2,6-dien-4-yn-1-al dissolved in toluene can be acylatedwithout isolation as described hereinafter. The toluene solution canalso be completely evaporated and the residue crystallized from dibutylether. The 2,6-dimethyl-S-hydroxy-octa- 2,6-dien-4-yn-1-al thus obtainedmelts at 32-34 C.

C. Preparation of Ester.

The 2,6-dimethyl-8-hydroxy-octa-2,6-dien-4-yn- 1 -a1 dissolved intoluene obtained according to above is, after theaddition of 180 ml. ofpyridine, treated with stirring at 0 to 10 C. with 85 ml. of acetylchloride in 100 ml. of toluene. After completion of the treatment, thereaction mixture is stirred at 20 to 25 C. for 30 minutes andsubsequently thoroughly shaken with 200 ml. of water. The toluene phaseis separated and successively washed at 20-25 C. with 300 m1; of 10percent aqueous sulphuric acid, 400 ml. of water and 200 ml. of water.The aqueous phase is separatedand again shaken out twice with'50 m1.,oftoluene each time. The combined toluene solutions are evaporated underreduced pressure at 60 C. The residual crude 2,6-dimethyl-8-acetoxy-octa-2,6-dien-4-yn-l-al can be purified bydistillation in high vacuum. The forerun going over at up to about 100C. [external temperature 120 internal pressure 0.03 Torr.] consistschiefly of 3- methyl-S-acetoxy-pent-3-en-l-yne. The pure 2,6-dimethyl-8-acetoxy-octa-2,6-dien-4-yn-l-al melts at 36 to 37 C.

D. Hydrogenation of Ester.

5.0 g. of 2,6-dimethyl-8-acetoxy-octa-2,6-dien-4-ynl-al are dissolved in30 m1. of toluene and, after the additionof 0.4 g. of apalladium/calcium carbonate cata-' lyst deactivated by addition of leadand quinoline [He1v. Chim. Acta. 35 (1952), 446], hydrogenated up to theuptake of 1.05 equivalents of hydrogen. The reaction solution, afterseparation 'of the catalyst, is successively washed with 0.5-N sulphuricacid, potassium hydrogen carbonate solution and water, then dried oversodium sulphate and treated with a solution of 0.02 g. of iodine in 2ml. of toluene. The solution is allowed to stand at room temperature for18 hours and is subsequently successively washed with a 5 percent sodiumthiosulphate solution and water, then dried over sodium sulphate andevaporated under reduced pressure. The residual2,6-dimethyl-8-acetoxy-octa- 2,4,6-trien-1-al melts at to 72 C. afterrecrystallization from ethyl ether/petroleum ether [boiling range 30 to40 C.].

EXAMPLE 21 hydrofuran and 100 ml. of benzene) was added at C within 20minutes a solution of 112.5 g. of trans-3- methyl-penten-(2)-yn-(4)-ol-(l) in 400 ml. of benzene.

The reaction mixture was kept under reflux conditions for one hour.Within one hour and while stirring 180 g. of orthoformic acid triethylester were then added dropwise and the resulting mixture refluxed forhours. The mixture was then poured into 2 kg. of ice and water andacidified to a pH of 6 by the addition of acetic acid. The benzene phasewas separated and washed with water. After evaporation of the benzenethere was obtained 6,6-diethoxy-3-methy1-hexen-(2)- yn-(4)-ol-(1) ofboiling point 115/O,l mm; n 1,4820; absorption maximum 225 muE 780.

B. Preparation of '6,6-diethoxy-3-methyl-hexadien- (2,4)-ol-(1) 39.6 g.of -6,6-diethoxy-3-methyl-hexen-(2)-yn-(4)- ol-(l) were dissolved in 200m1. of petroleum ether (boiling range 80-105) and 64 ml. of ethanol and,after the addition of 5,2 g. of a palladium/calcium carbonate catalystdeactivated by addition of lead and quinoline [Helv. Chim. Acta 35(1952), 446] and 6,4.

ml. of 3-pyridine-rnethanol, hydrogenated at 23C up to the uptake of 4,5l. of hydrogen. After separation of the catalyst and evaporation of thesolvent, the residue was distilled in a high vacuum. There was obtained:6,6- diethoxy-3-methyl-hexadien-(2,4)-o1-( 1) of boiling point9394C/0,02 mm; n 1,4777; absorption maximum 232 mu, E 3 617.

C. Preparation of 6-hydroxy-4-methyl-hexadien- (2,4)-al-( l) 1 96 g. of6,6-diethoxy-3-methylhexadien-(2,4)-ol-( l) were dissolved in 200 ml. ofether and treated with 10 ml. of 3N hydrochloric acid. The mixture wasstirred at room temperature for 20minutes and then treated with 20 g. ofpotassium carbonate. After filtration the fii- 'recristallisation fromisopropyl ether the aldehyde melted at 65 ,566,5C.

EXAMPLE 23 This Example is directed to the preparation of 8- acetoxy- 1l-diethoxy-2,6-dimethy1-octadien-( 2,6)- yne-(4), which is utilized asstarting material in Example 3.

A solution of 1 ml. of percent phosphoric acid and l g.ofp-toluene-sulfonic acid in 75 m1. of absolute ethanol was dropped to amixture of 206 g. of 8-acetoxy- 2,6-dimethyl-octadien-(2,6)-yn(4)-al-(l)and g. of orthoformic acid triethyl ester, whereby the mixture wasstirred, and by occasional cooling it was taken care that the reactiontemperature did not exceed 30C. The mixture was maintained at roomtemperature for 3 hours, then cooled to 0C, treated with 30 g. of sodiumhydrogen carbonate and stirred for 10 minutes. Additional 30 g. ofsodium hydrogen carbonate and 200 ml. of ice-water were then added andthe resulting mixture extracted with ether. The ether extract was washedtwice with ether, dried over potassium carbonate and concentrated invacuum. There was obtained 8- acetoxy-l ,1-diethoxy-2,6-dirnethyl-octadien-( 2 ,6 )-yn- (4)-al-( 1), boiling at 50/0,04 mm;absorption maxima: 263, 283 mu, E 810, 610.

We claim: 7

1. lO-Acetoxy-4,8-dimethyl-deca-trien-(2,4,8)-yn- 6-al-( l v 2. IlO-Acetoxy-4,8-dimethyl-deca-tetraen- (2,4,6,8)-al-(1).

3. lO-Hydroxy-4,8-dimethyl-deca-tetraen- (2,4,6,8)-al-(1). I

4. [3,7-dimethyl-lO oxo-deca-tetraen-(2,4,6,8)-yl]- tri-phenylphosphonium acid addition salt of an acid selected from the groupconsisting of hydrogen iodide, hydrogen bromide, hydrogen chloride andsulfuric acid.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 ,7 53 Dated June 2 1973 Inventor'(s) Hgg o Gutmarm and Ulrich Schwieter Itis certified that error appears in the above-identified patent and thatsaidlLetters Patent are hereby corrected as shown below:

Cover page,'af ter [21] Appl'. No.: 106,575, infsert:

[30] Foreign Application Priority Data January 21, 1966 switzerlandtuu...-856/66 Signed and sealed this ZO th 'day of August 1974; I

(SEAL) Attest: v I MCCOY M. GIBSON JR. (3. MARSHAL-L DANN Commissionerof Patents Attesting Officer 'USCOMM-DC 603764 09 U,S. GOVERNMENTPRINTING OFFICE: l9. 0-366-31",

FORM PO-105O (IO-69)

2. 10-Acetoxy-4,8-dimethyl-deca-tetraen-(2,4,6,8)-al-(1). 3.10-Hydroxy-4,8-dimethyl-deca-tetraen-(2,4,6,8)-al-(1). 4.(3,7-dimethyl-10-oxo-deca-tetraen-(2,4,6,8)-yl)-tri-phenyl phosphoniumacid addition salt of an acid selected from the group consisting ofhydrogen iodide, hydrogen bromide, hydrogen chloride and sulfuric acid.